A major cause of morbidity and mortality is the progression of organ damage associated with cardiovascular diseases. For instance, the incidence of stroke and costs associated with stroke damage continues to have a devastating impact on public health despite numerous treatments aimed at cardiovascular risk factors. Recent findings indicate that increasing levels of epoxides of arachidonic acid (EETs) appear to be new and excellent means to treat cardiovascular diseases. We demonstrated that in vivo inhibition of soluble epoxide hydrolase (SEH) resulted in higher levels of EETs and kidney protection in animal models of hypertension. More recently, we have conducted preliminary studies that suggest that SEH inhibitors can protect the brain from cerebral ischemic damage. Therefore, we will test the hypothesis that SEH inhibitors will have stroke damage protection that is due to decreased cerebral vascular injury and platelet aggregation. First, we will evaluate the ability of a newly developed orally active SEH inhibitor to prevent stroke damage associated with cardiovascular disease. Secondly, we will determine the effect of SEH inhibition on cerebral artery structure, endothelial function and platelet function in stroke-prone spontaneously hypertensive (SHRSP) rats. In the Phase II work, Arete Therapeutics will use the collected information to progress toward clinical trials in the area of stroke and possible new therapeutic avenues.